The hypophyseal portal system is inaccessible in humans, so direct in vivo measurements of pulsatile GnRH secretion are unavailable. However, LH pulses identified in the peripheral circulation correspond on a one- to- one basis with GnRH pulses identified in the hypophyseal portal system in animals (Figure 1); thus, LH (or α- subunit) pulse frequency— as determined by frequent peripheral blood sampling— accurately reflects GnRH pulse frequency. While LH (GnRH) pulse frequency approximates one pulse every 60– 90 minutes in the follicular phase, LH pulse frequency de creases to approximately one pulse every 3 to 8 hours during the luteal phase. In open loop conditions (e.g. surgical or natural menopause), LH pulse frequency approximates one pulse per hour. Similarly, isolated human mediobasal hypothalami generate a GnRH pulse every 60 to 100 minutes. Thus, a ‘circhoral’ (once per hour) pulse frequency may be a fundamental characteristic of the adult GnRH pulse generator, with changes reflecting the application or withdrawal of sex steroid (primarily progesterone) negative feedback. Since high and low GnRH pulse frequency preferentially favours LH and FSH secretion, respectively, cyclic changes in GnRH pulse frequency contribute to differential changes in LH and FSH concentrations across ovulatory cycles.
Fig1. Temporal relationship between pulses of GnRH in the pituitary portal system and pulses of LH in the peripheral circulation ( jugular vein). These data were obtained from a sheep model. Adapted with permission from Moenter SM, Brand RM, Midgley AR, Karsch FJ. Dynamics of gonadotropin- releasing hormone release during a pulse. Endocrinology 1992; 130:503– 10. (Ref 8) Copyright © 1992, Oxford University Press.
LH pulse amplitude can be modulated by changes of GnRH released per pulse, by changes of gonadotrope responses to GnRH stimulation, or both. LH pulse amplitude also varies inversely with the preceding LH interpulse interval. LH pulse amplitude tends to decrease across the follicular phase as a result of oestradiol negative feedback. However, the very high oestradiol concentrations at midcycle provoke increased gonadotropin release (the midcycle gonadotropin surge). During the luteal phase, LH pulse amplitudes are variable, but generally approximately double the amplitudes observed in the follicular phase.
In normally cycling women, circulating FSH concentrations are highest in the early part of follicular phase, wane across the follicular phase, but increase again as part of the midcycle gonadotropin surge. FSH concentrations remain relatively low during the luteal phase, but increase again at the luteal- follicular transition. The longer half- life of FSH tends to mask pulsatile release.
